Normal blood cell formation requires the production of both positive and negative regulators of hematopoiesis. With the hematopoietic microenvironment, cell to cell interactions appear to be important for the modulation of progenitor cell proliferation and differentiation. These cellular interactions involve the production of regulators of hematopoiesis. A control cell located within the hematopoietic microenvironment is the mononuclear phagocyte. This cell, which possesses diverse functional and secretory properties, interacts with other cells of the microenvironment to produce important products involved in the regulation of hematopoiesis. Among these are interleukin 1 and tumor necrosis factor. Interleukin 1 has been shown to be involved in a number of different functions concerning the inflammatory response; while tumor necrosis factor has been implicated in tumor cytotoxicity. How do these two important monocyte products affect hematopoiesis? The proposed studies will determine whether interleukin 1 plays an integral role in the production of stimulators of early hematopoiesis by cells of the hematopoietic microenvironment and whether other monokines, such as tumor necrosis factor, or lymphokines, such as gamma interferon, are also important in the positive and negative regulation of hematopoiesis.